Recent evidence has suggested that feedback from horizontal cells onto photoreceptors in the outer plexiform layer (OPL) of the vertebrate retina is modulated by a chemical transmitter, possibly GABA. The proposed research will focus on the development of the most advantageous vertebrate preparations for the study of this important aspect of neural interactions in the OPL. The system will be studied using selective pharmacological manipulations using agonists and antagonists of the natural transmitter such as aspartate, GABA, cobalt, picrotoxin or bicuculline along with physiological manipulations using suitable visual stimuli. Dual recording techniques will be applied to the study of independent neurons and their relationships simultaneously while passing currents before and during drug applications. Both standard perfusing and the nebulizer spray technique which was so useful to us in our experiments to better identify the rod photoreceptor transmitter in the vertebrate retina will be employed. Throughout this effort, we will draw heavily from experience with a similar study on the only other retinal system where neurotransmitter feedback onto photoreceptors has been established, the insect ocellar retina. Pharmacological studies of the ocellar retina, conducted almost exclusively in this laboratory over the past eight years, indicate important analogies with the vertebrate feedback system making it useful as a model comparable to having an isolated outer plexiform layer in the vertebrate retina. The suggestion from this system that lateral facilitation among second order neurons may be important not only to receptive field organization but also to the dynamics and stability of the feedback loop will be examined through uncoupling the electronically coupled horizontal cells in vertebrates and further studies of the ocellar retina as well. Anatomical investigations involving calcium binding sites and their role in synaptic transmission in the OPL will be continued in the retina of the skate.